Abstract PS4-07-26: Safety and efficacy of neoadjuvant cyclophosphamide, methotrexate, fluorouracil (CMF) and pembrolizumab in older adults with early triple negative breast cancer (TNBC)

Abstract Background: The current treatment of early-stage, locally advanced TNBC consists of neoadjuvant pembrolizumab, and a four-drug chemotherapy backbone, including paclitaxel, carboplatin, doxorubicin and cyclophosphamide, based on the KEYNOTE-522 trial. Many older adults are unable to receive this regimen due to comorbidities or performance status that increase their risk of toxicities. CMF is a chemotherapy regimen that is used in TNBC and safe with little long-term toxicity even in older patients. However, it has not been studied in combination with pembrolizumab, which was approved for early-stage TNBC in 2021. The goal of this study was to assess the safety and efficacy of neoadjuvant CMF and pembrolizumab in patients with early TNBC. Methods: We performed a retrospective chart review of all patients treated with neoadjuvant CMF and pembrolizumab for clinical Stage II-III TNBC from 2021-2024 at our institution’s health system. Demographics, tumor characteristics and treatment information were extracted from the electronic medical record. Toxicity of the regimen was measured by the percentage of patients requiring early discontinuation of one or more drugs, dose reductions, dose delays, hospitalizations, and/or emergency department (ED) visits due to treatment-related adverse events (TRAEs). Efficacy of the regimen was measured by the rate of pathologic complete response, defined as the absence of invasive disease in the breast and axilla at time of definitive surgery, in the overall population. Results: We identified 10 patients with early-stage, locally advanced TNBC who were treated with neoadjuvant CMF and pembrolizumab and included in the analysis. These patients were not eligible for the KEYNOTE-522 regimen due to performance status and/or comorbidities. The age at diagnosis of the patients ranged from 62 to 92 years with a median of 81 years. The median ECOG performance status was 1 (range 0-2) and 60% (N=6) had one or more comorbidities. Forty percent (N=4) of patients were Black. Most patients had Stage II disease (60%, N=6) and lymph node involvement (60%, N=6). The median number of cycles of CMF and pembrolizumab administered were 8 and 7, respectively. In terms of treatment toxicity, only one patient required a dose reduction in CMF due to neutropenic fever, discontinuation of pembrolizumab due to Grade 3 colitis, and hospitalization for these TRAEs. Twenty percent (N=2) had treatment delays due to Grade 2 adverse events but did not require dose reductions. There were no other drug discontinuations, hospitalizations or ED visits due to TRAEs. Of the 10 patients, 20% (N=2) have not undergone surgery yet due to comorbidities and insurance issues but both patients clinically had a treatment response based on exam. Of the remaining 8 patients with surgical information available, the pathologic complete response rate was 50%. Conclusions: The combination of neoadjuvant CMF and pembrolizumab was found to be well tolerated and effective in older patients with early TNBC who were ineligible to receive the KEYNOTE-522 regimen. While the findings are limited by their retrospective nature and small patient cohort, the preliminary safety and efficacy in a predominantly older population with comorbidities are promising and warrant further evaluation. A prospective phase II trial evaluating the combination of CMF and pembrolizumab is currently being planned. Citation Format: R. Patel, J. Anderson, R. Farley, A. Tiersten. Safety and efficacy of neoadjuvant cyclophosphamide, methotrexate, fluorouracil (CMF) and pembrolizumab in older adults with early triple negative breast cancer (TNBC) [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-07-26.